The present invention relates in general to mass spectrometers, and in particular to laser desorption/ionization time-of-flight mass spectrometers (“LDI-TOF-MS”).
Mass spectrometers can be excellent analytical tools for the detection and differentiation of analytes. As such, they have found increasing use in the analysis of biomolecules and, in particular, proteins. However, mass spectrometry has fallen short as a tool for quantitative biomolecular assays. This is mainly due to the fact that mass spectrometers do not perform with sufficient quantitative reproducibility from assay-to-assay. Furthermore, different mass spectrometers can produce different quantitative results given substantially similar samples and data acquisition protocols.
This drawback must be overcome if mass spectrometers are to become useful as assay platforms for proteins and, in particular, protein patterns. For example, scientists have found that protein profiles can provide better diagnostic power than single proteins in detecting disease. Mass spectrometers can be used to generate the protein profiles of both the afflicted individual and the reference populations, and a successful diagnosis is facilitated if the response of the mass spectrometers used are well matched. In particular, it is advantageous if the mass spectrometers used to generate protein profiles generate substantially similar masses and detected quantities for each protein present in substantially similar samples. It is further desirable that these results be of high quality, maximizing figures of merit such as signal-to-noise ratio and resolution. It is further desirable that the process of adjusting parameters to cause instruments to produce standard outputs be substantially automated.
Laser desorption time-of-flight mass spectrometry (TOF-MS) is particularly useful for protein profiling because it enables the detection of proteins with masses as high as hundreds-of-thousands of Daltons. This method involves using a laser to desorb and ionize analyte molecules from a surface, accelerating ions to a particular energy and then measuring the time required to traverse a free-flight path of fixed length to a detector. Since lighter ions arrive at the detector before heavier ions, a time record of the arrival times can then be converted into a mass spectrum. As is the case with most mass spectrometers, an LDI-TOF-MS includes three major components: (1) an ion source, (2) a mass analyzer, and (3) a detection system.